TGF‐β receptors: Assembly, signalling, and disease relevance

Abstract

TGF-β superfamily members exert their biological effects by binding to type I, type II and type III cell surface receptors. While the type I and type II receptors entail serine/threonine kinase domains and form signalling entities upon ligand binding, the type III receptors represent accessory receptors with no discernible kinase function identified to date. In TGF-β signalling, a heterotetrameric complex of the type I and II receptors is induced upon ligand binding, which promotes signal transduction through intracellular Smad proteins. Recent studies have indicated that type I and type II oligomerisation dynamics, which mainly serve to promote signalling purposes of TGF-β ligands, can also exert functional antagonism and negative regulation of ligand-induced signalling. The purpose of this review is to supply a detailed description of the TGF-β ligand-receptor network and oligomerisation patterns induced thereby, with special emphasis on the emerging and non-redundant roles of the accessory receptors of the TGF-β ligands in modulating receptor assembly and biological effects.